Dental pulp stem cell-derived small extracellular vesicle in irradiation-induced senescence
| Autor: | Hideharu Hibi, Yoshiro Koma, Hiroshi Maruyama, Kiyoshi Sakai, Jiao Dong, Junna Watanabe, Kohei Sakaguchi, Kehong Liu |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Senescence
Saliva medicine.medical_treatment Submandibular Gland Biophysics Biochemistry Andrology Superoxide dismutase Extracellular Vesicles Mice stomatognathic system medicine Acinar cell Animals Humans Molecular Biology Cellular Senescence Dental Pulp Inflammation Mice Inbred ICR Salivary gland biology Chemistry Stem Cells Cell Biology Extracellular vesicle respiratory system Disease Models Animal Oxidative Stress medicine.anatomical_structure Cytokine Gamma Rays biology.protein Female Stem cell Signal Transduction |
| Zdroj: | Biochemical and biophysical research communications. 575 |
| ISSN: | 1090-2104 |
| Popis: | Small extracellular vesicles (sEV) facilitate signaling molecule transfer among cells. We examined the therapeutic efficacy of human dental pulp stem cell-derived sEV (hDPSC-sEV) against cellular senescence in an irradiated-submandibular gland mouse model. Seven-week-old mice were exposed to 25 Gy radiation and randomly assigned to control, phosphate-buffered saline (PBS), or hDPSC-sEV groups. At 18 days post-irradiation, saliva production was measured; histological and reverse transcription-quantitative PCR analyses of the submandibular glands were performed. The salivary flow rate did not differ significantly between the PBS and hDPSC-sEV groups. AQP5-expressing acinar cell numbers and AQP5 expression levels in the submandibular glands were higher in the hDPSC-sEV group than in the other groups. Furthermore, compared with non-irradiated mice, mice in the 25 Gy + PBS group showed a high senescence-associated-β-galactosidase-positive cell number and upregulated senescence-related gene (p16INK4a, p19Arf, p21) and senescence-associated secretory phenotypic factor (MMP3, IL-6, PAI-1, NF-κB, and TGF-β) expression, all of which were downregulated in the hDPSC-sEV group. Superoxide dismutase levels were lower in the PBS group than in the hDPSC-sEV group. In summary, hDPSC-sEV reduced inflammatory cytokine and senescence-related gene expression and reversed oxidative stress in submandibular cells, thereby preventing irradiation-induced cellular senescence. Based on these results, we hope to contribute to the development of innovative treatment methods for salivary gland dysfunction that develops after radiotherapy for head and neck cancer. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect